CDC14B explained
Dual specificity protein phosphatase CDC14B is an enzyme that in humans is encoded by the CDC14B gene.[1] [2]
The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. This protein is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, which suggests the role in cell cycle control. Specifically, it is thought to fulfil this role by bundling and stabilising microtubules. This protein has been shown to interact with and dephosphorylates tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splicing of this gene results in 3 transcript variants encoding distinct isoforms.
Interactions and Functions
CDC14B has been shown to interact with p53, potentially de-phosphorylate p53 at Serine 315 and thereby stabilize p53.[3] S315-phosphorylated p53, in contrast to other p53 phosphorylation, was shown to facilitate p53 degradation.[4] At the patho-physiological level, mice with CDC14B deletion were shown to exhibit early-onset ageing phenotypes. [5]
Further reading
- Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . vanc .
- Li L, Ljungman M, Dixon JE . The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53 . The Journal of Biological Chemistry . 275 . 4 . 2410–2414 . January 2000 . 10644693 . 10.1074/jbc.275.4.2410 . free .
- Mailand N, Lukas C, Kaiser BK, Jackson PK, Bartek J, Lukas J . Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation . Nature Cell Biology . 4 . 4 . 317–322 . April 2002 . 11901424 . 10.1038/ncb777 . vanc . 28955777 .
- Kaiser BK, Zimmerman ZA, Charbonneau H, Jackson PK . Disruption of centrosome structure, chromosome segregation, and cytokinesis by misexpression of human Cdc14A phosphatase . Molecular Biology of the Cell . 13 . 7 . 2289–2300 . July 2002 . 12134069 . 117313 . 10.1091/mbc.01-11-0535 .
- Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA . Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle . Molecular and Cellular Biology . 23 . 9 . 3173–3185 . May 2003 . 12697818 . 153197 . 10.1128/MCB.23.9.3173-3185.2003 . vanc .
- Gray CH, Good VM, Tonks NK, Barford D . The structure of the cell cycle protein Cdc14 reveals a proline-directed protein phosphatase . The EMBO Journal . 22 . 14 . 3524–3535 . July 2003 . 12853468 . 165618 . 10.1093/emboj/cdg348 .
- Nalepa G, Harper JW . Visualization of a highly organized intranuclear network of filaments in living mammalian cells . Cell Motility and the Cytoskeleton . 59 . 2 . 94–108 . October 2004 . 15362113 . 10.1002/cm.20023 .
- Cho HP, Liu Y, Gomez M, Dunlap J, Tyers M, Wang Y . The dual-specificity phosphatase CDC14B bundles and stabilizes microtubules . Molecular and Cellular Biology . 25 . 11 . 4541–4551 . June 2005 . 15899858 . 1140622 . 10.1128/MCB.25.11.4541-4551.2005 . vanc .
- Vázquez-Novelle MD, Esteban V, Bueno A, Sacristán MP . Functional homology among human and fission yeast Cdc14 phosphatases . The Journal of Biological Chemistry . 280 . 32 . 29144–29150 . August 2005 . 15911625 . 10.1074/jbc.M413328200 . free . 10366/157107 . free .
Notes and References
- Li L, Ernsting BR, Wishart MJ, Lohse DL, Dixon JE . A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast . The Journal of Biological Chemistry . 272 . 47 . 29403–29406 . November 1997 . 9367992 . 10.1074/jbc.272.47.29403 . free .
- Web site: Entrez Gene: CDC14B CDC14 cell division cycle 14 homolog B (S. cerevisiae).
- Li L, Ljungman M, Dixon JE . The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53 . The Journal of Biological Chemistry . 275 . 4 . 2410–2414 . January 2000 . 10644693 . 10.1074/jbc.275.4.2410 . free .
- Li . Y . Cui K. Zhang Q . Li X . Lin X . Tang Y . Prochownik E . Li Y . July 2021 . FBXL6 degrades phosphorylated p53 to promote tumor growth . Cell Death Differ. . 28 . 7 . 2112–2125 . 1350-9047. 33568778 . 10.1038/s41418-021-00739-6 . 8257708 . free .
- Wei Z, Peddibhotla S, Lin H, Fang X, Li M, Rosen M, Zhang P . Early-onset aging and defective DNA damage response in Cdc14b-deficient mice . Mol. Cell. Biol. . 31 . 7 . 1470–1477 . April 2011 . 21262768 . 10.1128/MCB.01330-10 . 3135283 . free .